The
discovery and development of new drugs to provide medicines for treating
diseases is the main role of the pharmaceutical industry. It is a challenging and
expensive activity of pharmaceutical industry. Biological organisms and
especially human beings are extraordinarily complex, and our understanding of
how they function at the molecular level remains rudimentary, although
considerable advances in knowledge have been made in recent decades. Whilst an
advanced industrial society was able to plan and deliver a man to the moon
following a 10-year program, almost 50 years on we are still only able to treat
about 60% of cancer patients effectively, and do not understand how to correct
most mental diseases. Development of new medicines is complex, time consuming
and very expensive. The average cost of developing a new drug is estimated to
be about US $ 1-1.2 billion, including expenditures on failed projects. This
amount is about four times the price of an Airbus A380 at US $ 270 million, or
five times that of a Boeing B - 787 Dreamliner at US $ 200 million.
Total drug development time grew from an average of 8.1 years in the 1960s to 11.6 years in the 1970s, to 14.2 in the 1980s, to 15.3 years for drugs approved from 1990 through 1995. Pharmaceutical companies and regulatory authorities are working together to reduce this time span. With the advent of technologies in biological screening procedures of new chemical entities the time involved in drug discovery has gone down in recent years but the cost of drug discovery has touched a new high. Success rate in getting from an initial compound to an approved and commercially available product is very low. Typically, tens of thousands of compounds are screened and tested, and only a handful makes it onto the market as drug products. The statistics are such that, out of the 10,000 compounds that show initial promise, only 0.3% will reach the testing stage for sub-acute study, five will go into human clinical trials, and only one will become an approved drug.
|
Drug
Discovery |
Drug
Developments |
|
1. Program
selection (choosing a disease to work on) 2. Identification
and validation a drug target 3. Assay
development 4. Identification
of a “lead compound” 5. Lead
optimization 6. Identification
of a drug candidate |
1. Preclinical
study 2. Clinical
trials 3. Release
of the drug 4. Follow-up
monitoring
|
The process involves finding out the target that causes the disease. Next, chemical or biological compounds are screened and tested against these targets or assays, which are representative of these targets, to find leading drug candidates for further development. Many new scientific approaches are now used to determine targets (most targets are receptors or enzymes) and obtain the lead compounds; including the use of genomic technology, synthetic chemistry, recombinant DNA (rDNA) technology, laboratory automation and bioinformatics. Tests are performed on the lead compounds in test tubes (in vitro) and on animals (in vivo) to check how they affect the biological systems. The tests, often called preclinical research activities, include toxicology, pharmacodynamics and pharmacokinetics, as well as optimization of drug delivery systems. The leading compounds are modified and synthesized to improve their interactions with the targets, or to reduce the toxicity or improve pharmacokinetics performance. At the end of this process, an optimized compound is found and this becomes a potential drug ready for clinical trial in human. The development work has to follow Good Laboratory Practice (GLP) to ensure that proper quality system and ethical considerations are established. Only compounds that satisfy certain performance and safety criteria will proceed to the next stage of clinical trial. Then release of the drug occurs and follow up monitoring is required for confirming the effectiveness of the drug.
Figure
1: Drug discovery and development processes.
After
completion of preclinical studies successfully, the investigators files an ‘Investigational
New Drug’ application (IND) to the government bodies such as Central Drugs
Standard Control Organization (CDSCO), for allowance of initial
testing in human beings. After the successful clinical trials and laboratory
work, the investigators may file a New Drug Application (NDA). Permission to
market a drug product will be given by the drug control authority after
confirming the drug’s safety and effectiveness.
